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Non-Canonical Wnt Signaling Pathways

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...

Non-Canonical Wnt Signaling Pathways

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...

Canonical Wnt Signaling Pathway

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...

Canonical Wnt Signaling Pathway

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...

Master Transcription Regulators

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

The JAK-STAT Signaling Pathway

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...

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Investigation of Beige Fat Biology and Metabolism Using the CRISPR SunTag-p65-HSF1 Activation System

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Published on: January 6, 2023

WISP2 regulates preadipocyte commitment and PPARγ activation by BMP4.

Ann Hammarstedt¹, Shahram Hedjazifar, Lachmi Jenndahl

¹Lundberg Laboratory for Diabetes Research, Center of Excellence for Metabolic and Cardiovascular Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.

Proceedings of the National Academy of Sciences of the United States of America

|January 30, 2013

Summary

WISP2, a novel adipokine, plays a key role in hypertrophic obesity and metabolic syndrome by regulating fat cell differentiation. Its activation in subcutaneous adipose tissue identifies metabolic syndrome in obese individuals.

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Last Updated: May 14, 2026

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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

Area of Science:

Adipose tissue biology
Metabolic syndrome research
Cell signaling pathways

Background:

Hypertrophic obesity results from enlarged fat cells, leading to inflammation and metabolic dysfunction.
WNT1 inducible signaling pathway protein 2 (WISP2) and WNT pathway activation markers are elevated in hypertrophic human abdominal adipose tissue.
Increased visceral fat and insulin resistance are associated with hypertrophic obesity.

Purpose of the Study:

To investigate the role of WISP2 in hypertrophic obesity and metabolic syndrome.
To elucidate the mechanism by which WISP2 regulates adipogenesis and adipose tissue function.
To identify WISP2 as a potential biomarker for metabolic syndrome.

Main Methods:

Analysis of WISP2 expression in human abdominal subcutaneous adipose tissue.
In vitro studies using 3T3-L1 cells, human preadipocytes, and NIH 3T3 fibroblasts.
Knockdown and mutant protein expression experiments to assess WISP2 function.
Investigation of WISP2 interaction with BMP4, SMAD, Zfp423, and PPARγ signaling pathways.

Main Results:

WISP2 expression is increased in hypertrophic obesity and linked to insulin resistance.
WISP2 activation in subcutaneous adipose tissue, but not visceral fat, identifies metabolic syndrome.
WISP2 knockdown promotes adipocyte differentiation; WISP2 inhibits differentiation by forming a complex with Zfp423, preventing PPARγ activation.
BMP4 dissociates the WISP2-Zfp423 complex, enabling Zfp423 nuclear translocation and PPARγ activation for adipogenesis.

Conclusions:

Adipogenic commitment and differentiation are regulated by cross-talk between BMP4 and WNT signaling, with WISP2 as a key regulator.
WISP2 is a novel adipokine linking hypertrophic obesity and the metabolic syndrome.
WISP2 may serve as a diagnostic marker for metabolic syndrome in obese individuals.